Assessing Barriers to Primary Prevention of Cardiovascular Diseases in Low and Middle-Income Countries: A Systematic Review.

The incidence of cardiovascular diseases (CVDs) in low- and middle-income countries (LMICs) has greatly increased. Previously dominated by infectious diseases, LMICs are the new epicentre of CVDs. CVD is a common problem amongst the population in the African continent; however, many countries in LMICs lack the resources to stem the rise of CVDs. A systematic review was conducted between March and July 2023 to assess barriers to the primary prevention of CVDs in studies conducted in LMICs. Online databases, such as Embase, Cochrane, Scopus, and MEDLINE, were consulted. Keywords included primary prevention, cardiovascular diseases, diabetes, weight loss, and physical fitness, all of which focused on LMICs. To enrich the literature review, efforts were made to check other listed references and more papers were retrieved. The inclusion criteria were countries in LMICs, CVD, full-text, and peer-reviewed journals. Qualitative and quantitative studies were included. Exclusion criteria included high-income countries, secondary prevention, and research unrelated to CVDs, such as barriers in oncology or mental health. A total of 1089 papers were retrieved from the search engines. After applying the exclusion criteria for LMICs, only 186 papers were retained. A further search for quality, relevance, and duplicity reduced the qualifying number to 50 papers. Further efforts to retrieve the data and examine the quality of the studies resulted in 18 final selected studies. Three categories emerged based on the type of barriers: physician barriers, patient barriers, and health system barriers. Evidently, in several LMICs, guidelines for CVD prevention were lacking, and too much emphasis was placed on secondary prevention at the expense of primary prevention, a lack of human resources, and inadequate infrastructure. Overworked healthcare providers were unable to allocate adequate time to the patients. There was no shared decision-making process. Patient barriers included lack of motivation, no symptoms, low level of education, no insurance, long physical distances to the facilities, and inadequate medication or stock out. Some of the major barriers included closing and opening hours, poor operating space, inadequate funding from the government or donors, and lack of electronic medical services. There are many barriers to accessing primary prevention services for CVDs. These barriers can be divided into patient, physician, or health system barriers. More research needs to be conducted in LMICs to address the increasing risk factors for CVDs. Greater investment is required by national governments to provide more resources. Task shifting and shared decision-making are some of the quick wins.

Experience of safety monitoring in the context of a prospective observational study of artemether-lumefantrine in rural Tanzania: lessons learned for pharmacovigilance reporting.

OBJECTIVES: To identify and implement strategies that help meet safety monitoring requirements in the context of an observational study for artemether-lumefantrine (AL) administered as first-line treatment for uncomplicated malaria in rural Tanzania. METHODS: Pharmacovigilance procedures were developed through collaboration between the investigating bodies, the relevant regulatory authority and the manufacturer of AL. Training and refresher sessions on the pharmacovigilance system were provided for healthcare workers from local health facilities and field recorders of the Ifakara Health Demographic Surveillance System (IHDSS). Three distinct channels for identification of adverse events (AEs) and serious adverse events (SAEs) were identified and implemented. Passive reporting took place through IHDSS and health care facilities, starting in October 2007. The third channel was through solicited reporting that was included in the context of a survey on AL as part of the ALIVE (Artemether-Lumefantrine In Vulnerable patients: Exploring health impact) study (conducted only in March-April 2008). RESULTS: Training was provided for 40 healthcare providers (with refresher training 18 months later) and for six field recorders. During the period 1st September 2007 to 31st March 2010, 67 AEs were reported including 52 under AL, five under sulphadoxine-pyrimethamine, one under metakelfin, two after antibiotics; the remaining seven were due to anti-pyretic or anti-parasite medications. Twenty patients experienced SAEs; in 16 cases, a relation to AL was suspected. Six of the 20 cases were reported within 24 hours of occurrence. DISCUSSION: Safety monitoring and reporting is possible even in settings with weak health infrastructure. Reporting can be enhanced by regular and appropriate training of healthcare providers. SMS text alerts provide a practical solution to communication challenges. CONCLUSION: Experience gained in this setting could help to improve spontaneous reporting of AEs and SAEs to health authorities or marketing authorization holders.

Adherence to and acceptability of artemether-lumefantrine as first-line anti-malarial treatment: evidence from a rural community in Tanzania.

BACKGROUND: Controlled clinical trials have shown that a six-dose regimen of artemether-lumefantrine (AL) therapy for uncomplicated Plasmodium falciparum malaria results in cure rates >95% with good tolerability. MATERIALS AND METHODS: A prospective study was carried out to document the adherence to and acceptability of AL administration. This was undertaken in the context of the ALIVE study, a prospective, community-based, observational study in a rural, malaria-endemic area of Tanzania. Following microscopic confirmation of P. falciparum infection, the first AL dose was taken under supervision, with the subsequent five doses taken unsupervised at home. Patients were randomized to receive a home-based assessment close to the scheduled time for one of the unsupervised doses, but were blinded to which follow-up visit they had been allocated. A structured questionnaire was administered by trained staff and AL consumption was confirmed by inspection of blister packs. RESULTS: A total of 552 patients were recruited of whom 352 (63.8%) were <13 years old. The randomization process allocated 112, 109, 110, 100 and 111 patients to a follow-up visit after doses 2, 3, 4, 5 and 6, respectively. For dose 2, 92.0% of patients (103/112) correctly took AL at 8 +/- 1 hours after dose 1. The remaining doses were taken within four hours of the correct time in 87-95% of cases. Nine patients (1.7%) missed one dose. Blister packs were available for inspection in 548 of cases (99.3%) and confirmed patient-reported data that the previous dose had been administered. Nearly all patients took AL with water (549/552 [99.5%]). Two patients (0.4%) took the drug with food. The dosing pictogram and clustering of tablets within the blister packs was considered helpful by 91.8% and 100.0% of patients, respectively. Overall, 87.1% of patients (481/552) found AL easier to take/administer than sulphadoxine-pyrimethamine (SP) and 87.7% (484/552) believed that AL was more effective than SP. DISCUSSION: Factors contributing to adherence were likely to be helpful packaging, pictorial dosing instructions and patients' conviction that AL is effective. CONCLUSION: Adherence to the dosing regimen and timing of AL administration was very good.

Deploying artemether-lumefantrine with rapid testing in Ethiopian communities: impact on malaria morbidity, mortality and healthcare resources.

OBJECTIVE: To assess the impact and feasibility of artemether-lumefantrine deployment at community level, combined with phased introduction of rapid diagnostic tests (RDTs), on malaria transmission, morbidity, and mortality and health service use in a remote area of Ethiopia. METHODS: Two-year pilot study in two districts: artemether-lumefantrine was prescribed after parasitological confirmation of malaria in health facilities in both districts. In the intervention district, artemether-lumefantrine was also made available through 33 community health workers (CHWs); of these, 50% were equipped with RDTs in the second year. RESULTS: At health facilities; 54 774 patients in the intervention and 100 535 patients in the control district were treated for malaria. In the intervention district, 75 654 patients were treated for malaria by community health workers. Use of RDTs in Year 2 excluded non-Plasmodium falciparumin 89.7% of suspected cases. During the peak of malaria transmission in 2005, the crude parasite prevalence was 7.4% (95% CI: 6.1-8.9%) in the intervention district and 20.8% (95% CI: 18.7-23.0%) in the control district. Multivariate modelling indicated no significant difference in risk of all-cause mortality between the intervention and the control districts [adjusted incidence rate ratio (aIRR) 1.03, 95%CI 0.87-1.21, P = 0.751], but risk of malaria-specific mortality was lower in the intervention district (aIRR 0.60, 95%CI 0.40-0.90, P = 0.013). CONCLUSIONS: Artemether-lumefantrine deployment through a community-based service in a remote rural population reduced malaria transmission, lowered the malaria case burden for health facilities and reduced malaria morbidity and mortality during a 2-year period which included a major malaria epidemic.

The content of African diets is adequate to achieve optimal efficacy with fixed-dose artemether-lumefantrine: a review of the evidence.

A fixed-dose combination of artemether-lumefantrine (AL, Coartem(R)) has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat.As the fat content of sub-Saharan African meals is approximately a third that of Western countries, it raises the question of whether fat consumption by African patients is sufficient for good efficacy. Data from healthy volunteers have indicated that drinking 36 mL soya milk (containing only 1.2 g of fat) results in 90% of the lumefantrine absorption obtained with 500 mL milk (16 g fat). African diets are typically based on a carbohydrate staple (starchy root vegetables, fruit [plantain] or cereals) supplemented by soups, relishes and sauces derived from vegetables, pulses, nuts or fish. The most important sources of dietary fat in African countries are oil crops (e.g. peanuts, soya beans) and cooking oils as red palm, peanut, coconut and sesame oils. Total fat intake in the majority of subSaharan countries is estimated to be in the range 30-60 g/person/day across the whole population (average 43 g/person/day). Breast-feeding of infants up to two years of age is standard, with one study estimating a fat intake of 15-30 g fat/day from breast milk up to the age of 18 months. Weaning foods typically contain low levels of fat, and the transition from breast milk to complete weaning is associated with a marked reduction in dietary fat. Nevertheless, fat intake >10 g/day has been reported in young children post-weaning. A randomized trial in Uganda reported no difference in the efficacy of AL between patients receiving supervised meals with a fixed fat content (~23 g fat) or taking AL unsupervised, suggesting that fat intake at home was sufficient for optimal efficacy. Moreover, randomized trials in African children aged 5-59 months have shown similar high cure rates to those observed in older populations, indicating that food consumption is adequate post-weaning. In conclusion, it appears that only a very small amount of dietary fat is necessary to ensure optimal efficacy with AL and that the fat content of standard meals or breast milk in sub-Saharan Africa is adequate.